Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies to polymerized human albumin (poly-HSA) could not be detected by using sensitive methods (enzyme-linked immunosorbent assay and radioimmunoprecipitation) in sera from chronic carriers of hepatitis B surface antigen (HBsAg) or in serial bleedings from one chimpanzee infected with type A hepatitis virus and one infected with non-A, non-B hepatitis virus. By a solid-phase radioimmunoassay, receptor sites for poly-HSA could be detected on HBsAg particles from sera containing either hepatitis B "e" antigen (HBeAg) or anti-HBe. Blocking experiments showed that monomeric HSA did not bind to this receptor. In general, the HBsAg particles from sera with HBeAg had more poly-HSA receptor sites or relatively more particles carrying this receptor compared with HBsAg from sera with anti-HBe. Microtiter plates coated with poly-HSA bound HBsAg from sera containing HBeAg with greater efficiency than did anti-HBs coupled to a solid phase (Ausria II beads), whereas with sera positive for anti-HBe, the two assays were equally sensitive. Decreased ability of HBsAg to bind to poly-HSA was seen in some sera which had been stored for a few years at 4 degrees C, whereas the binding to anti-HBs was unaffected. It is possible that polymers of albumin on the surface of hepatocytes could function as receptors for hepatitis B virus.
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PMID:Sites that bind polymerized albumin on hepatitis B surface antigen particles: detection by radioimmunoassay. 50 Jan 99

HBsAg is known to bind to human serum albumin polymerized by glutaraldehyde, human serum albumin has been found in preparations of HBsAg by several investigators. However, it is not yet known whether natural human serum albumin binds to hepatitis B virus under physiological conditions. We studied the binding between natural or recombinant HBsAg and monomeric human serum albumin by immunological, biochemical and biophysical methods. The binding capacity of 20-nm HBs spheres was variable but ranged up to six molecules HSA/sphere. A reversible binding site for human serum albumin was exclusively localized in the preS2 domain, whereas the S domain was inactive in vitro. Human serum albumin copurified with HBsAg of human origin during gel chromatography or sucrose-gradient centrifugation. This human serum albumin was monomeric in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The preS2-bound part of the human serum albumin could be removed from HBsAg by high-salt, such as CsCl centrifugation, but another part could only be removed by treatment with a disulfide cleaving reagent. Most of this covalently bound human serum albumin was retained at the HBsAg particle after complete cleavage of medium-sized HBs protein with trypsin. This indicates a second way in which albumin binds irreversible to cysteine(s) of the small HBs protein (SHBs, P24 and GP27).
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PMID:Interaction between hepatitis B surface proteins and monomeric human serum albumin. 216 67

The binding of polyalbumin to hepatitis B virus (HBV)-associated envelope epitopes has been studied by means of a radioimmunoprecipitation technique. HBV particles were purified from the sera of chronic hepatitis B surface antigen (HBsAg) carriers and labelled through the endogenous HBV-DNA polymerase reaction. Human albumin, polymerized through glutaraldehyde cross-linking, was able to precipitate (100%) labelled HBV at concentrations of 31.2 and 62.5 micrograms/ml, in contrast to monomeric albumin (HSA). This event was further confirmed by immune electron microscopy. The addition of anti-HSA to the mixture HBV plus polyalbumin gave a 100% precipitation in a wide dilution range (15.6-500 micrograms/ml). The binding of polyalbumin (31.2 micrograms/ml) to virions was strongly inhibited (up to 98%) when preincubating with antibody to a glycosylation-dependent preS2 epitope on HBV. The same was accounted (up to 99%) for polyvalent IgG anti-HBs. However, antibodies to the group 'a' and subtype 'd' determinants, as well as anti-preS1 region antibodies, inhibited weakly polyalbumin binding to HBV. The binding site of the inhibitory antibody overlaps probably with neutralizing epitopes. Our findings support the hypothesis that albumin binding plays an important role in the viral life cycle.
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PMID:Inhibition of albumin binding to hepatitis B virions by monoclonal antibody to the preS2 domain of the viral envelope. 245 8

There are four polypeptides coded for by the region Pre-S and gene S on DNA of hepatitis B virus that carry the receptor for polymerized human serum albumin (poly-HSA), i.e., P31 and P39, as well as their glycosylated counterparts P35 and P43. With the use of monoclonal antibodies directed to Pre-S(1) sequence and Pre-S(2) sequence (bearing the receptor for poly-HSA), the content of these polypeptides, as well as their expression on the surface, was determined for hepatitis B particles of various categories. P39 and P43, carrying both Pre-S(1) and Pre-S(2) sequences, were contained abundantly in Dane and tubular particles, and to a much lesser extent in small spherical particles, all of which were purified from plasma containing hepatitis B e antigen (HBeAg). P31 and P35, carrying Pre-S(2) but not Pre-S(1) sequence, were contained comparably in these three categories of hepatitis B particles. In remarkable contrast, small spherical particles derived from plasma containing antibody to HBeAg were very low in the content of any Pre-S polypeptides. P31 and P39 showed higher activities for poly-HSA receptor than their glycosylated versions. When Dane particles were digested with trypsin, the poly-HSA receptor was deprived in parallel with the loss of antigenicity for Pre-S(2) sequence. The antigenicity for Pre-S(1) sequence was much less affected, and that for the product of gene S was virtually unchanged by the digestion.
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PMID:Polypeptides coded for by the region pre-S and gene S of hepatitis B virus DNA with the receptor for polymerized human serum albumin: expression on hepatitis B particles produced in the HBeAg or anti-HBe phase of hepatitis B virus infection. 300 21

Hepatitis B markers were studied in seven patients with reactivated liver disease. Reactivation of chronic type B hepatitis, as indicated by the reappearance of hepatitis B e antigen (HBeAg) in the serum, was characterised by the appearance of hepatitis B virus-DNA (HBV-DNA) in the serum. The expression of pre-S 1 encoded protein remained unchanged in five of seven patients, and poly-HSA as a marker for pre-S 2 encoded protein remained detectable in six of seven patients before and after reactivation of chronic hepatitis. The level of serum HBV-DNA correlated well with the level of liver enzymes, which rose from normal to various levels after reactivation of the liver disease. The data suggest that inflammatory activity of the liver disease is not related to the expression of pre-S encoded protein but to viral replication. Possibly pre-C and C-gene encoded antigens, which are produced together with viral nucleic acid and expressed on the surface of HBV-infected liver cells, play the key role in liver damage believed to be mediated by cytotoxic T cells.
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PMID:Reactivation of chronic type B hepatitis: the effect on expression of serum HBV-DNA and pre-S encoded proteins. 339 23

The use of glutaraldehyde as a coupling reagent in the passive hemagglutination test (HA) has gained wide application, especially for the coating of red blood cells (RBC) with glutaraldehyde-polymerized human serum albumin (pHSA), for studies of the albumin receptor on hepatitis B surface antigen (HBsAg) or for the detection of anti-albumin antibodies (AAA). Here we report a previously unrecognized reactivity with glutaraldehyde-treated RBC mainly with sera from patients with liver disease. The highest incidences of this reaction were found in patients with acute viral hepatitis A and B, namely 44 of 50 (88%) and 31 of 50 (62%) respectively. In 234 HBsAg carriers the frequency was low (3%). This reactivity was also observed in 19 of 50 sera from patients with chronic liver disease documented by biopsy, but not in sera from 68 healthy subjects. By immunofluorescence on glutaraldehyde-treated RBC it was shown that the corresponding antibodies belonged mainly to the IgM class. In all HBsAg-negative patients studied the HA titer against glutaraldehyde-treated RBC was in agreement with the titer against RBC coated with pHSA or pBSA (polymerized bovine serum albumin). Absorption with pHSA abolished the reaction with glutaraldehyde-treated RBC in 7 of 8 sera, suggesting a common reactivity between glutaraldehyde-polymerized HSA and glutaraldehyde-treated RBC. Apart from the possible clinical importance of these antibodies, their existence is a possible source of false positive results when glutaraldehyde is used as a coupling reagent for immunological assays, in particular with sera from patients with liver diseases.
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PMID:Reactivity of sera from patients with liver disease with glutaraldehyde-treated erythrocytes: role for false positive results in hemagglutination tests. 642 47

We constructed a plasmid that directs the synthesis and secretion of hepatitis B virus (HBV) surface antigen (HBsAg) particles by Saccharomyces cerevisiae. This plasmid contains a proteinase-resistant HBsAg M (M-P31c) gene fused at its 5'-terminus with a chicken-lysozyme signal peptide (C-SIG) gene, which is placed under the yeast GLD (glyceraldehyde-3-phosphate dehydrogenase gene) promoter. The products encoded by the "C-SIG+M-P31c" (LM-P31c) gene were synthesized and assembled themselves into HBsAg particles in yeast cells, and the particles were released into the medium along with poly-HSA (polymerized human serum albumin) binding activity. The HBsAg particles purified from the medium were very similar in density (1.19 g cm-3), size (19.2 +/- 0.8 nm in diameter) and shape (sphere) to human-plasma-derived HBsAg particles. When several sec (temperature-sensitive secretion-defective) mutants were used as host cells, the release of HBsAg particles into the medium was blocked at 37 degrees C but not at 25 degrees C, indicating that the HBsAg particles are exported through the normal yeast secretion pathway. To our knowledge, this is the first report that yeast cells are capable of secreting particles into the medium.
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PMID:Saccharomyces cerevisiae can release hepatitis B virus surface antigen (HBsAg) particles into the medium by its secretory apparatus. 776 88

Adenine arabinoside monophosphate (ara-AMP) is a potent antiviral agent against hepadnaviruses but its use in the treatment of chronic hepatitis B is hampered by severe neurotoxic side effects, which are dose dependent. In order to reduce these adverse reactions and to adopt the lysosomotropic approach to antiviral chemotherapy, ara-AMP was coupled to lactosaminated human serum albumin (L-HSA), a neoglycoprotein which specifically penetrates hepatocytes. In mice with Ectromelia virus hepatitis, ara-AMP coupled with L-HSA was selectively delivered to liver cells in which it was released in a pharmacologically active form. Moreover in woodchucks with WHV hepatitis and in patients with chronic HBV infection, coupled ara-AMP inhibited hepadnavirus replication at a dose (1.5 mg/kg/day) 3-6 times lower than the free drug. A clinical study using a 28-day period of treatment with conjugated ara-AMP at 1.5 mg/kg/day has now been started. In the first 6 patients the treatment has been completed. The conjugate inhibited virus growth without producing any side effects. L-HSA-ara-AMP conjugate must be given by intravenous infusion. New hepatotropic conjugates of ara-AMP have been recently prepared which could be administered by bolus intravenous injection or by intramuscular route. These complexes might assure a better compliance in patients with hepatitis B virus infection for a long lasting liver targeted antiviral treatment.
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PMID:Liver targeting of adenine arabinoside monophosphate (ara-AMP) by coupling to lactosaminated human serum albumin. 852 36

Dideoxycytidine (ddC) is a nucleoside analogue active against human immunodeficiency virus and with in vitro activity against human hepatitis B virus. We investigated the ability of ddC to inhibit one of the Hepadnaviridae, the woodchuck hepatitis virus and compared the results with the effect obtained by a conjugate of lactosaminated human serum albumin 2',-3'-dideoxycytidine monophosphate (L-HSA ddCMP). This compound specifically enters the hepatocyte via the asialoglycoprotein receptor. We treated five chronic woodchuck hepatitis virus carriers with intravenous injections of 0.5 mg/kg body weight of ddC for 5 consecutive days, and under the same protocol five woodchucks with 10.4 mg/ kg L-HSA ddCMP, a dose equivalent to 0.25 mg/kg of free ddC. A reduction of serum woodchuck hepatitis virus DNA (5-125 fold) was observed during therapy in three out of five animals receiving ddC and in two of the five animals treated with L-HSA ddCMP. In responding woodchucks, virus DNA levels rebounded immediately after stopping therapy. No signs of toxicity were observed during or after the course of therapy. These preliminary results of short-term treatment indicate that ddC has anti-viral activity against woodchuck hepatitis virus. When the dose was reduced by 50%, L-HSA ddCMP showed anti-viral activity to an even lesser degree.
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PMID:Treatment of woodchuck hepatitis virus infection in vivo with 2', -3'-dideoxycytidine (ddC) and 2',-3'-dideoxycytidine monophosphate coupled to lactosaminated human serum albumin (L-HSA ddCMP). 874 Aug 40

In order to reduce the extrahepatic side-effects of antiviral nucleoside analogues in the treatment of chronic viral hepatitis, these drugs are conjugated with galactosyl-terminating macromolecules. The conjugates selectively enter hepatocytes after interaction of the carrier galactose residues with the asialoglycoprotein receptor present in large amounts and high affinity only on these cells. Within hepatocytes the conjugates are delivered to lysosomes where enzymes split the bond between the carrier and the drug, allowing the latter to become concentrated in the liver. The validity of this chemotherapeutic strategy has been endorsed by a clinical study. Adenine arabinoside monophosphate (ara-AMP), conjugated with lactosaminated human serum albumin (L-HSA) and administered to hepatitis B virus (HBV)-infected patients for 28 days, exerted an antiviral activity to the same extent as the free drug without producing any clinical side-effects, including the severe neurotoxicity caused by the free drug. Preclinical studies are now underway with conjugates obtained using lactosaminated poly-L-lysine (Lac-poly(Lys)) as the hepatotropic carrier. These new conjugates have some advantages over those prepared with L-HSA: they can be administered by the intramuscular route; they are obtained entirely by chemical synthesis, thus eliminating the problems involved in the use of haemoderivatives; they have a heavy drug load, which permits administration of smaller quantities of conjugate that are more easily digested in lysosomes; and they enable higher quantities of drug to be introduced into hepatocytes. The results of the experiments with two Lac-poly(Lys) conjugates, one with ara-AMP and one with ribavirin, are reported in this review.
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PMID:Liver targeting of antiviral nucleoside analogues through the asialoglycoprotein receptor. 943 Mar 55


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